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Open Access Research article

Relating gene expression evolution with CpG content changes

Huan Yang1, Dawei Li2 and Chao Cheng34*

Author Affiliations

1 Department of Gynecology, The Ninth People’s Hospital of Chongqing, Chongqing 400700, China

2 Department of Microbiology and Molecular Genetics, College of Medicine, Burlington VT 05405, USA

3 HB7400, Remsen 702, Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover NH 03755, USA

4 Institute for Quantitative Biomedical Sciences, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon NH 03766, USA

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BMC Genomics 2014, 15:693  doi:10.1186/1471-2164-15-693

Published: 20 August 2014



Previous studies have shown that CpG dinucleotides are enriched in a subset of promoters and the CpG content of promoters is positively correlated with gene expression levels. But the relationship between divergence of CpG content and gene expression evolution has not been investigated. Here we calculate the normalized CpG (nCpG) content in DNA regions around transcription start site (TSS) and transcription terminal site (TTS) of genes in nine organisms, and relate them with expression levels measured by RNA-seq.


The nCpG content of TSS shows a bimodal distribution in all organisms except platypus, whereas the nCpG content of TTS only has a single peak. When the nCpG contents are compared between different organisms, we observe a different evolution pattern between TSS and TTS: compared with TTS, TSS exhibits a faster divergence rate between closely related species but are more conserved between distant species. More importantly, we demonstrate the link between gene expression evolution and nCpG content changes: up-/down- regulation of genes in an organism is accompanied by the nCpG content increase/decrease in their TSS and TTS proximal regions.


Our results suggest that gene expression changes between different organisms are correlated with the alterations in normalized CpG contents of promoters. Our analyses provide evidences for the impact of nCpG content on gene expression evolution.